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新药研究与开发班级学号：122042239姓名：闫洁日期：2015.10.27Drug Experimentation in Healthy Volunteers1.IntroductionDrug development is a complex process that includes drug discovery/productdevelopment, pre-clinical research (in vitro/in vivo) and clinical trials. The new chemicalentities, which show promising pharmacodynamic activity in in vitro experiments onparticular biological targets, thought to play critical pathophysiological roles in specificdiseases, emerge from the process of drug discovery and are candidates to undergo safetyand toxicity tests, as well as pharmacokinetic and metabolism evaluations in in vivo preclinical models. Moreover, pre-clinical investigations are focused on determining the doseand administration schedule to be used in the first human clinical trial (first-in-man or firsthuman dosing).健康志愿者的药物试验1．介绍药物开发是一个复杂的过程,包括药物发现/产品发展，临床前研究(体外/体内)和临床试验。新的化学实体,在体外实验显示前景开阔的药效学活性特定的生物指标，认为发挥重要的病理生理作用疾病出现在药物发现过程中，候选人接受安全和毒性测试以及在体内药代动力学和代谢评估临床前任务。此外,临床前研究的重点是确定剂量和管理计划中使用第一个临床试验（第一次作用于人体或第一的人）。Clinical drug development is currently arranged into four phases, with phase I traditionallyrepresenting the very early stage of drug development in humans. Phase I is conducted toestablish safety and tolerability, to evaluate pharmacokinetics and to obtain preliminarydata on pharmacodynamics. Phase I begins with the first administration of a new compoundin humans (Pocock, 1983).临床药物开发目前安排分为四个阶段,第一阶段是传统代表药物在人类发展的早期阶段，建立安全性和耐受性,评估药物动力学和获得初步药效学数据。新的化合物在第一阶段的第一次给药是人类(Pocock,1983)。Based on differences in the experimental design, various types of phase I trials can bedistinguished: (1) Single ascending dose studies, in which small groups of subjects receive asingle dose of the test drug, afterward they are observed and examined for a given period oftime. If subjects do not experience any remarkable adverse effect, and pharmacokinetic data are roughly consistent with pre-specified safety values, the dose is escalated up, and a newgroup of subjects is then given a higher dose (Buoen et al